Although combination antiretroviral therapy (ART) has been successful in suppressing plasma HIV RNA levels in infected patients, it has not resulted in eradication of virus. Prolonged, continuous ART results in significant toxicities and difficulties adhering to drug regimens. In addition, the cost of antiretroviral drugs is prohibitive for many individuals and countries. Therefore, we have studied the virologic and immunologic effects of intermittent versus continuous ART in HIV-infected individuals in an attempt to reduce the total time an individual receives therapy while maintaining therapeutic efficacy. To test the need for and feasibility of strict adherence to a short-cycle intermittent ART regimen, we are currently conducting a randomized, controlled trial of short cycle (5 days on, 2 days off) intermittent therapy versus continuous ART in Kampala, Uganda (Protocol 02-I-N288, A Randomized, Controlled Trial of Short Cycle Intermittent versus Continuous HAART for the Treatment of Chronic HIV Infection in Uganda). The study originally included a 7/7 arm (7 days on, 7 days off) but was discontinued because several patients failed specific study criteria. Patients initially enrolled in the 7/7 arm were transferred to continuous therapy and are being monitored for the original duration of the study (73 weeks). The study enrollment and follow-up have been completed with 146 patients total;32 in the 7/7 arm, 57 in the 5/2 arm and 57 in the continuous arm. The analysis of virologic outcomes is currently focused on comparing the 5/2 and continuous study arms. The main primary outcome analysis is complete and the manuscript has been submitted to the Journal of Infectious Diseases. The antiretroviral resistance data was published in Antiviral Therapy and is included in the bibliography below. Baseline characteristics were similar between study arms. Six patients in the 5/2 arm and 8 in the continuous arm reached a failure endpoint before study completion. Two patients in the continuous arm met end-of-study failure criterion at week 73 (VL of 553 and 4394). In the 5/2 arm 6 failed and 46/52 (88.5%) of the remaining patients successfully completed study compared to the continuous arm where 11 failed and 39/49 (79.6%) patients successfully completed the study. The upper 97.5% confidence limit for the difference between the percent of non-failures in the 5/2 arm versus continuous was 4.8% (preset margin 15%). No significant difference in the time to failure was found in the 2 study arms. In summary, short cycle intermittent ART may be an important option for the treatment of HIV infection to reduce cost and, possibly, toxicity while potentially enhancing adherence. If safety and efficacy of short-cycle intermittent therapy is ultimately demonstrated in clinical settings, it might prove to be an important strategy to expand therapy in resource-limited settings.